Since its introduction into clinical medicine, the tricyclic antidepressant drug, imipramine, has become a mainstay in the management of depressed patients. However, reports in the literature indicate its association with cardiac complications such as ventricular arrhythmias, conduction abnormalities and ST-T wave abnormalities. Although the literature itself is contradictory, a major difficulty in evaluating the cardiac effects of tricyclic drugs is the marked interindividual variation in plasma drug concentration. This study will clarify the pharmacological and toxic effects of imipramine on the heart by simultaneously monitoring plasma drug concentration of imipramine with its effects on the electrocardiogram, i.e., heart rate, conduction and arrhythmias. Frequent 24-hour continuous ECG monitoring and computer analysis will allow us to accumulate and analyze an enormous amount of electrocardiographic data which we will correlate with plasma concentrations of imipramine, desmethylimipramine, and the hydroxylated metabolites. In this way, we will characterize drug concentration and cardiac effect as well as identify ECG characteristics associated with greater risk to developing untoward drug induced effects. Ultimately this study will allow us to gain predictive value in selecting the patients who will be likely to tolerate imipramine without adverse effects and thereby enhance its rational use.